Fibroblast growth factor receptor signaling in cardiomyocytes is protective in the acute phase following ischemia-reperfusion injury.
Fibroblast growth factor receptor signaling in cardiomyocytes is protective in the acute phase following ischemia-reperfusion injury.
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DOI：
10.3389/fcvm.2022.1011167
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发表时间：
2022
影响因子：
3.6
通讯作者：
Ornitz, David M.
中科院分区：
文献类型：
--
作者：
Matsiukevich, Dzmitry;House, Stacey L.;Weinheimer, Carla;Kovacs, Attila;Ornitz, David M.
关键词：
成纤维细胞生长因子受体（FGFR）在成人心脏的多种细胞类型中表达。先前的研究已经显示了一些FGF配体在心脏缺血-再灌注（I/R）损伤中的心脏保护作用以及内皮FGFR在缺血后血管重塑中的保护作用。为了确定FGFR信号在急性心脏I/R损伤中心肌细胞中的直接作用，我们在I/R损伤之前在成年小鼠的心肌细胞中灭活Fgfr 1和Fgfr 2（CM-DCKO）或激活FGFR 1（CM-caFGFR 1）。在没有损伤的情况下，成年心肌细胞中Fgfr 1和Fgfr 2的失活对心脏形态学或功能没有影响。当受到I/R损伤时，与对照组相比，CM-DCKO小鼠在再灌注后1天的心肌细胞死亡显著增加，并且在再灌注后7天的梗死面积、心功能障碍和心肌细胞肥大增加。没有观察到基因型依赖性效应对缺血后心肌细胞横截面积和远离梗死区域的血管密度的影响。相比之下，心肌细胞中FGFR 1信号在缺血发作前的短暂激活并不影响再灌注后1天和7天心脏I/R损伤后的结果。这些数据表明，内源性细胞自主性心肌细胞FGFR信号传导支持心肌细胞在心脏I/R损伤后的急性期存活，并且这种心脏保护导致心脏重塑期间持续改善的结果。结合一些FGF配体和内皮FGFR信号传导在I/R损伤中的既定保护作用，本研究支持开发促进I/R损伤后心肌细胞FGF信号传导的治疗策略。
Fibroblast growth factor receptors (FGFRs) are expressed in multiple cell types in the adult heart. Previous studies have shown a cardioprotective effect of some FGF ligands in cardiac ischemia-reperfusion (I/R) injury and a protective role for endothelial FGFRs in post-ischemic vascular remodeling. To determine the direct role FGFR signaling in cardiomyocytes in acute cardiac I/R injury, we inactivated Fgfr1 and Fgfr2 (CM-DCKO) or activated FGFR1 (CM-caFGFR1) in cardiomyocytes in adult mice prior to I/R injury. In the absence of injury, inactivation of Fgfr1 and Fgfr2 in adult cardiomyocytes had no effect on cardiac morphometry or function. When subjected to I/R injury, compared to controls, CM-DCKO mice had significantly increased myocyte death 1 day after reperfusion, and increased infarct size, cardiac dysfunction, and myocyte hypertrophy 7 days after reperfusion. No genotype-dependent effect was observed on post-ischemic cardiomyocyte cross-sectional area and vessel density in areas remote to the infarct. By contrast, transient activation of FGFR1 signaling in cardiomyocytes just prior to the onset of ischemia did not affect outcomes after cardiac I/R injury at 1 day and 7 days after reperfusion. These data demonstrate that endogenous cell-autonomous cardiomyocyte FGFR signaling supports the survival of cardiomyocytes in the acute phase following cardiac I/R injury and that this cardioprotection results in continued improved outcomes during cardiac remodeling. Combined with the established protective role of some FGF ligands and endothelial FGFR signaling in I/R injury, this study supports the development of therapeutic strategies that promote cardiomyocyte FGF signaling after I/R injury.
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DOI：
10.1016/j.bbrc.2018.06.161
发表时间：
2018-09-18
影响因子：
3.1
作者：
Fang, Yuan;Zhao, Yan;Yuan, Zuyi
通讯作者：
Yuan, Zuyi
影响因子：
10.8
作者：
Huang, Chahua;Liu, Yang;Schultz, Jo El J.
通讯作者：
Schultz, Jo El J.
影响因子：
5.5
作者：
Khosravi F;Ahmadvand N;Bellusci S;Sauer H
通讯作者：
Sauer H
影响因子：
4
作者：
Itoh N;Ohta H
通讯作者：
Ohta H
影响因子：
5
作者：
Manning JR;Wijeratne AB;Oloizia BB;Zhang Y;Greis KD;Schultz JEJ
通讯作者：
Schultz JEJ